Low-Calorie Sweeteners with Carbohydrate Do Not Impair Insulin Sensitivity in Humans: Re-analysis Highlighting the Importance of the Comparator

We read with interest the report by Dalenberg et al., 2020Dalenberg J.R. Patel B.P. Denis R. Veldhuizen M.G. Nakamura Y. Vinke P.C. Luquet S. Small D.M. Short-term consumption of sucralose with, but not without, carbohydrate impairs neural and metabolic sensitivity to sugar in humans.Cell Metab. 2020; 31: 493-502.e7Abstract Full Text PDF PubMed Scopus (45) Google Scholar a series clinical experiments test “sweet uncoupling hypothesis” using low-calorie sweetener (LCS) sucralose. The main conclusion was that failed confirm incidentally demonstrated combination LCS carbohydrate, alone, insulin (Dalenberg Scholar). feel data do support these conclusions owing several methodological considerations. choice comparators makes it difficult disentangle effect from carbohydrates or their combination. authors compared three groups: (sucralose), (120 kcal sucrose), combo maltodextrin + sucralose), each fed over 10 days. Sucrose selected as sweet caloric comparator matched non-sweet which could be combined. These sources are very different compositions effects. is disaccharide consisting 50% glucose fructose used sweetener. Maltodextrin, on other hand, short-chain polymer sports drinks bulking agent. Whereas rapidly hydrolyzed small intestine absorbed via sodium-linked transporter-1 (SGLT-1) rate absorption similar greater than pure (Hofman 2016Hofman D.L. van Buul V.J. Brouns F.J.P.H. Nutrition, health, regulatory aspects digestible maltodextrins.Crit. Rev. Food Sci. Nutr. 2016; 56: 2091-2100Crossref (72) Scholar), sucrose into its components latter more slowly easily saturable transporter-5 (GLUT-5) further GLUT-2 presence co-ingested (Kellett 2008Kellett G.L. Brot-Laroche E. Mace O.J. Leturque A. Sugar intestine: role GLUT2.Annu. 2008; 28: 35-54Crossref (310) It well established fate glucose. Unlike glucose, bypasses rate-limiting step glycolysis (phosphofructokinase-1) only portion converted (<25%) (Khan Sievenpiper, 2016Khan T.A. Sievenpiper J.L. Controversies about sugars: results systematic reviews meta-analyses obesity, cardiometabolic disease diabetes.Eur. J. 55: 25-43Crossref (106) Fructose, therefore, has minimal impact postprandial insulin, leptin, ghrelin doses have also been shown catalytic disposal through upregulation glucokinase, decreasing glycemic response (Braunstein 2020Braunstein C.R. Noronha J.C. Khan Mejia S.B. Wolever T.M.S. Josse R.G. Kendall C.W.C. Effect epimers metabolism: review meta-analysis.Clin. 39: 3308-3318Abstract (5) result marked differences blood glucose-raising ability reflected low index (low GI) (GI = 20), intermediate GI 62), high 100) scale (Rytz 2019Rytz Adeline D. Lê K.-A. Tan Lamothe L. Roger O. Macé K. Predicting load macronutrients accelerate development foods beverages lower responses.Nutrients. 2019; 11: 1172Crossref (9) There fMRI signals between (Page 2013Page K.A. Chan Arora Belfort-Deaguiar Dzuira Roehmholdt B. Cline G.W. Naik Sinha Constable R.T. Sherwin R.S. Effects vs regional cerebral flow brain regions involved appetite reward pathways.JAMA. 2013; 309: 63-70Crossref (251) acute can translate longer term metabolism. Furthermore, isocaloric substitution for starch Scholar) improve control, while low-GI high-GI (Livesey 2019Livesey G. Taylor Livesey H.F. Buyken A.E. Jenkins D.J.A. Augustin L.S.A. Barclay A.W. Liu al.Dietary risk type 2 diabetes: assessment causal relations.Nutrients. 1436Crossref (44) both control sensitivity. contend based physiological were sufficiently question whether Experiment 1. difference Combo groups may entirely explained content absence LCS. plausible alone lack higher would resulted responses. In recognizing suitable rule out an group, conducted another experiment (Experiment 3) they assessed within-treatment (pre versus post) design without group. concluded because no seen pre- post-treatment ruled out, so 1 must owe group alone. Although we commend undertaking 3, this approach analysis highly misleading (Bland Altman, 2011Bland J.M. Altman D.G. Comparisons against baseline within randomised often misleading.Trials. 2011; 12: 264Crossref (112) By restricting comparison, one does know if non-significant increase 3 significant To isolate maltodextrin, appropriate direct comparison two 2015Bland Best (but oft forgotten) practices: testing treatment effects randomized trials separate analyses changes approach.Am. Clin. 2015; 102: 991-994Crossref (77) necessity comparisons treatments drawing inferences endorsed CONSORT (http://www.consort-statement.org/checklists/view/32-consort-2010/66-title), Cochrane (https://training.cochrane.org/handbook/current/chapter-03), guidance major international authorities including Drug Administration (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/e9-statistical-principles-clinical-trials). set re-analyze compare (maltodextrin sucralose). extracted individual incremental areas under curve (iAUC) participant figures paper Plot Digitizer (https://sourceforge.net/projects/plotdigitizer/). Figure S1 shows our box whisker plot iAUC Sugar, LCS, Combo, groups. reproducing authors’ exact STATA 16.1, did find any change 0–30 min (p 0.401) 0–120 0.247). As sample size normal distribution assumed, performed pairwise permutation 1,000 resamples replacement bootstrap all resulting p values reliable distributional assumption. Using second method, 0.329) 0.230). show affect cannot out. conclusion, allow Our re-analysis showed responses groups, suggesting likely mediated avoid potential confounding future research designs, investigators consider instead retaining comparator. T.A.K. received Canadian Institutes Health Research (CIHR), Carbohydrates International Life Science Institute (ILSI), National Honey Board , Bee Maid Ltd . He invited speaker at Calorie Control Council Annual Meeting, he honorarium. J.L.S. Foundation Innovation, Ontario Fund, Province Ministry Innovation Science, Diabetes Canada, PSI Foundation, Banting Centre (BBDC), American Society Nutrition (ASN), INC Nut Dried Fruit Trade Association, Board, Sciences Pulse Quaker, Tate Lyle Nutritional Fund University Toronto, Glycemic Cardiovascular Disease Type Toronto (a fund Alberta Growers), Trialists inaugural donation Council). in-kind food donations controlled trial Almond California, California Walnut Commission, Peanut Council, Barilla, Unilever, Upfield, Unico/Primo, Loblaw Companies, Kellogg WhiteWave Foods, Nutrartis. travel support, fees, and/or honoraria Dairy Farmers FoodMinds LLC, Sweeteners Nestlé, Endocrinology Metabolism (CSEM), Abbott, General Mills, Biofortis, ASN, Northern School Medicine, & Education European Safety Authority (EFSA), Comité Européen des Fabricants de Sucre (CEFS), Physicians Committee Responsible Medicine. had ad hoc consulting arrangements Perkins Coie LLP, Lyle, Wirtschaftliche Vereinigung Zucker e.V., Danone, Inquis Clinical Research. member Juice Association Scientific Expert Panel Soy (SNI) Advisory Committee. Practice Guidelines Committees Study (EASD), (CCS), Obesity Canada. serves served unpaid scientific advisor Food, Program (FNSP) Technical ILSI North America. Carbohydrate Quality Consortium (ICQC), Executive Member Group (DNSG) EASD, Director 3D Knowledge Synthesis Trials foundation. His wife employee AB InBev. Download .pdf (.15 MB) Help pdf files Document S1. Further Evidence Habitual Consumption Sucralose Not Alters Glucose MetabolismDalenberg al.Cell MetabolismFebruary 02, 2021In BriefIn letter, al. provide point-by-point critique offered Kahn Sievenpiper. They offer new evidence original finding study mice. Full-Text